Evidence map›Paper›PMID 9087451›Full record

ArticleThe Journal of cell biology1997

Integrin-mediated activation of MAP kinase is independent of FAK: evidence for dual integrin signaling pathways in fibroblasts.

T H Lin, A E Aplin, Y Shen, Q Chen, M Schaller, L Romer, I Aukhil, R L Juliano

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in The Journal of cell biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
12.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 244 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Infection and immunity · 2019
    Article
  5. The Inhibitory Role of α2,6-Sialylation in Adipogenesis.The Journal of biological chemistry · 2017
    Article
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  13. Aberrant differentiation of fibroblast progenitors contributes to fibrosis in the aged murine heart: role of elevated circulating insulin levels.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013
    Article
  14. Review
  15. Netrin-1 attracts axons through FAK-dependent mechanotransduction.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012
    Article
  16. mTORC1 inhibition and ECM-cell adhesion-independent drug resistance via PI3K-AKT and PI3K-RAS-MAPK feedback loops.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2012
    Article
  17. Article
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4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

T H LinDepartment of Pharmacology, University of North Carolina, Chapel Hill 27599, USA.
A E Aplin
Y Shen
Q Chen
M Schaller
L Romer
I Aukhil
R L Juliano
University of North Carolina at Chapel Hill · US

Funding

THE ROLE OF RAP1 IN INTEGRIN ACTIVATION AND PLATELET SIGNALINGP01HL045100 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PARISE, LESLIE V. · 1993 to 2007
$13.7M
NHLBI NIH HHS HL03299NHLBI NIH HHS P01 HL045100NIGMS NIH HHS GM26065
6 · The paper itself

Abstract

Integrin-mediated cell adhesion causes activation of MAP kinases and increased tyrosine phosphorylation of focal adhesion kinase (FAK). Autophosphorylation of FAK leads to the binding of SH2-domain proteins including Src-family kinases and the Grb2-Sos complex. Since Grb2-Sos is a key regulator of the Ras signal transduction pathway, one plausible hypothesis has been that integrin-mediated tyrosine phosphorylation of FAK leads to activation of the Ras cascade and ultimately to mitogen activated protein (MAP) kinase activation. Thus, in this scenario FAK would serve as an upstream regulator of MAP kinase activity. However, in this report we present several lines of evidence showing that integrin-mediated MAP kinase activity in fibroblasts is independent of FAK. First, a beta1 integrin subunit deletion mutant affecting the putative FAK binding site supports activation of MAP kinase in adhering fibroblasts but not tyrosine phosphorylation of FAK. Second, fibroblast adhesion to bacterially expressed fragments of fibronectin demonstrates that robust activation of MAP kinase can precede tyrosine phosphorylation of FAK. Finally, we have used FRNK, the noncatalytic COOH-terminal domain of FAK, as a dominant negative inhibitor of FAK autophosphorylation and of tyrosine phosphorylation of focal contacts. Using retroviral infection, we demonstrate that levels of FRNK expression sufficient to completely block FAK tyrosine phosphorylation were without effect on integrin-mediated activation of MAP kinase. These results strongly suggest that integrin-mediated activation of MAP kinase is independent of FAK and indicate the probable existence of at least two distinct integrin signaling pathways in fibroblasts.

Indexed as

Adaptor Proteins, Signal Transducing3T3 CellsAnimalsCalcium-Calmodulin-Dependent Protein KinasesCell AdhesionCell Adhesion MoleculesChickensEnzyme ActivationFibroblastsFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesGRB2 Adaptor ProteinIntegrin beta1MicePeptide FragmentsPoint MutationAdaptor Proteins, Signal TransducingCalcium-Calmodulin-Dependent Protein KinasesCell Adhesion MoleculesFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesGRB2 Adaptor ProteinGrb2 protein, mouseIntegrin beta1Peptide FragmentsProteinsProtein-Tyrosine KinasesPtk2 protein, mouseRecombinant Fusion Proteins

Identifiers

PMID9087451
PMCPMC2132513
OpenAlexW2144130192

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.